rs5402

Positions:

• chr3-171009950-T-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000340.2(SLC2A2):​c.496+8A>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.134 in 1,540,942 control chromosomes in the GnomAD database, including 20,411 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.22 (5347 hom., cov: 30)
  • Exomes 𝑓: 0.12 (15064 hom.)
• Consequence: SLC2A2 NM_000340.2 splice_region, intron
• Scores: Splicing: ADA: 0.00001880
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -1.31

Genes affected

SLC2A2 (HGNC:11006): (solute carrier family 2 member 2) This gene encodes an integral plasma membrane glycoprotein of the liver, islet beta cells, intestine, and kidney epithelium. The encoded protein mediates facilitated bidirectional glucose transport. Because of its low affinity for glucose, it has been suggested as a glucose sensor. Mutations in this gene are associated with susceptibility to diseases, including Fanconi-Bickel syndrome and noninsulin-dependent diabetes mellitus (NIDDM). Alternative splicing results in multiple transcript variants of this gene. [provided by RefSeq, Jul 2013]

ENSG00000286856 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 3-171009950-T-A is Benign according to our data. Variant chr3-171009950-T-A is described in ClinVar as [Benign]. Clinvar id is 130350.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-171009950-T-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.45 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC2A2	NM_000340.2	c.496+8A>T		splice_region_variant, intron_variant		ENST00000314251.8	NP_000331.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC2A2	ENST00000314251.8	c.496+8A>T		splice_region_variant, intron_variant		1	NM_000340.2	ENSP00000323568.3

Frequencies

GnomAD3 genomes AF: 0.221 AC: 33244 AN: 150672 Hom.: 5330 Cov.: 30

Gnomad AFR AF: 0.456

Gnomad AMI AF: 0.0757

Gnomad AMR AF: 0.176

Gnomad ASJ AF: 0.143

Gnomad EAS AF: 0.00914

Gnomad SAS AF: 0.149

Gnomad FIN AF: 0.126

Gnomad MID AF: 0.138

Gnomad NFE AF: 0.132

Gnomad OTH AF: 0.196

GnomAD3 exomes AF: 0.0892 AC: 16621 AN: 186318 Hom.: 1810 AF XY: 0.0882 AC XY: 8853 AN XY: 100346

Gnomad AFR exome AF: 0.378

Gnomad AMR exome AF: 0.0740

Gnomad ASJ exome AF: 0.0927

Gnomad EAS exome AF: 0.00250

Gnomad SAS exome AF: 0.0966

Gnomad FIN exome AF: 0.0748

Gnomad NFE exome AF: 0.0801

Gnomad OTH exome AF: 0.0912

GnomAD4 exome AF: 0.125 AC: 173204 AN: 1390152 Hom.: 15064 Cov.: 38 AF XY: 0.125 AC XY: 86113 AN XY: 690020

Gnomad4 AFR exome AF: 0.460

Gnomad4 AMR exome AF: 0.115

Gnomad4 ASJ exome AF: 0.134

Gnomad4 EAS exome AF: 0.0141

Gnomad4 SAS exome AF: 0.143

Gnomad4 FIN exome AF: 0.120

Gnomad4 NFE exome AF: 0.117

Gnomad4 OTH exome AF: 0.138

GnomAD4 genome AF: 0.221 AC: 33292 AN: 150790 Hom.: 5347 Cov.: 30 AF XY: 0.219 AC XY: 16099 AN XY: 73588

Gnomad4 AFR AF: 0.456

Gnomad4 AMR AF: 0.176

Gnomad4 ASJ AF: 0.143

Gnomad4 EAS AF: 0.00917

Gnomad4 SAS AF: 0.149

Gnomad4 FIN AF: 0.126

Gnomad4 NFE AF: 0.132

Gnomad4 OTH AF: 0.194

Alfa AF: 0.147 Hom.: 586

Bravo AF: 0.238

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 10, 2015	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Mar 05, 2013	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Fanconi-Bickel syndrome Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

not provided Benign:2

Benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Oct 22, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.049
DANN	Benign	0.47

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000019
dbscSNV1_RF	Benign	0.0
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs5402; hg19: chr3-170727739;